Nerve growth factor (NGF) is synthesized and secreted by two cell lines derived from the nervous system, the rat C6 glioma and the mouse NB2A neuroblastoma. The content of NGF is increased in either cell line by agents which elevate cyclic AMP, beta-adrenergic receptor agonists for the glioma cells and prostaglandin El or adenosine for the neuroblastoma. The increase of cyclic AMP and concomitant activation of protein kinase does not increase the net synthesis of NGF, but rather appears to activate a peptidase which may form NGF from a pro-NGF. Research is being carried out to determine 1) the characteristics of the glioma cell protein kinase(s); 2) the precise mechanism by which protein kinase activates the peptidase and 3) the biochemical characteristics of the precursor NGF.